Comparable outcomes of BTK inhibitors and fixed-duration venetoclax plus rituximab in second-line treatment of chronic lymphocytic leukaemia: a real-world analysis by the Czech CLL study group

Abstract In relapsed/refractory (RR) chronic lymphocytic leukaemia (CLL), Bruton tyrosine kinase inhibitors (BTKi) are administered as monotherapy until disease progression. In contrast, venetoclax, a B-cell lymphoma 2 (BCL-2) protein inhibitor, is typically combined with rituximab (VenR) as a time-limited regimen. To date, neither randomized nor retrospective trials have directly compared these approaches in RR CLL, and only limited data are available comparing venetoclax plus obinutuzumab (VenObi) to BTKi in the first-line setting. We retrospectively analysed 352 patients receiving second-line therapy: 93 VenR and 259 BTKi (ibrutinib: n = 222; acalabrutinib: n = 37). Baseline characteristics were well balanced, except for a higher incidence of TP53 mutation and trisomy 12 in BTKi-treated patients. At a median follow-up of 13.8 months (VenR) and 22.1 months (BTKi), 12-month progression-free survival (PFS) and overall survival (OS) were comparable (PFS: 85.1% vs. 82.2%, p = 0.265; OS: 87.6% vs. 88.4%, p = 0.291). Estimated median PFS (45.4 vs. 37.9 months, p = 0.265) and OS (83.6 vs. 74.2 months, p = 0.291) also showed no significant differences between the VenR and BTKi cohorts. Treatment discontinuation due to adverse events before month 24 was more frequent with BTKi (22.5% with VenR vs. 34.3% with BTKi), primarily due to infections (10.6% vs. 28.6%) and disease progression (14.3% vs. 22.5%). These preliminary data suggest comparable outcomes and manageable toxicity profiles for both regimens.